Validation of Difficult Airway Physiological Score (DAPS) in Critically Ill Adults Undergoing Endotracheal Intubation in the Emergency Department

Background Critically ill patients have increased risk of cardiovascular collapse following endotracheal intubation due to physiological instability. This study aims to validate the Difficult Airway Physiological Score (DAPS) in adults to predict the risk of serious outcomes in the emergency department of a tertiary care private hospital. Methods This is a cohort study conducted in the emergency department (ED) from 2021 to 2022. Difficult Airway Physiological Score (DAPS) was derived from a sample of 1021 patients through a retrospective study. The variables in the score were age, gender, time of intubation, vitals and vomiting at presentation, pH <7.3, fever, physician's anticipation for patient decline, and agitation. The model performance was assessed prospectively on a separate dataset (n = 326) using train-test split method. Postintubation desaturation, hypotension, cardiac arrest, and mortality postintubation were the serious outcomes. ROC analysis, sensitivity, specificity, PPV, and NPV were used to assess score validity. Results Our study includes 326 patients, of which 123 (37.7%) were males and 203 (62.2%) were females. The sample was divided into high-risk (DAPS ≥10) group, n = 194 with mean age of 52 (SD = ±18) years, and low-risk (DAPS <10) group, n = 132 with mean age of 47.7 (SD = ±17.4) years. The shock index ≥0.9 was in 128 (66%), while it was <0.9 in low-risk n = 111 (84%), p value <0.001. Similarly, pH <7.3 was seen in 70 (36.1%) in high-risk group compared to 4 (3%) in low-risk group, p value <0.001. Cardiac arrest was observed in 56 (17.2%) patients, of which 45 (23.2%) were in high-risk and 11 (8.3%) in low-risk groups (p < 0.001). Hypotension was the primary outcome in the high-risk group 100 (51.5%) versus 32 (24.2%) in low-risk group (p < 0.001). The DAPS of 10 had an area under the curve of 0.865 (0.71–0.84). The sensitivity of DAPS was 78.5%, specificity 77.9%, and accuracy 78.2%. Conclusion The score can accurately predict serious outcomes in critically ill adult patients with physiologically difficult airway demonstrating good sensitivity and specificity.


Background
Te proportion of difcult intubation ranges from 10% to 27% in emergency department compared to 1% to 9% in the operating room [1].Studies show 28% of acutely ill patients undergoing endotracheal intubation experience lifethreatening complications like hypoxemia, hypotension, airway trauma, and cardiac arrest [2,3].Furthermore, the incidence of difcult intubation is signifcantly increased in the emergency department due to critical illness, which increases the risk of adverse events [4].Endotracheal intubation in a critically ill adult with physiological instability is associated with many anticipated and unanticipated challenges [5].Te physiologically difcult airway is defned as an airway in which an adult with severe physiological abnormalities (hypotension-defned as systolic blood pressure <90 mmHg, severe metabolic acidosis-defned as pH <7.3, and hypoxia-defned as peripheral oxygen saturation <92% and right heart failure) had an increased risk of cardiovascular collapse or mortality after intubation or during transition to positive pressure ventilation [5,6].
Te data for successful intubation and peri-intubation complications are limited from developing countries [7].Early identifcation of physiologically difcult intubation can help clinicians attempt early stabilization and hence reducing the risk of serious outcomes like hypotension, cardiac arrest, mortality, and hypoxia.However, unlike anatomically difcult airways, there is a paucity of scores that can predict serious outcomes in physiologically difcult airways [8][9][10].Tree scores are currently reported in the literature that addresses physiological instability variables in their difcult airway assessment scores [11][12][13].Tese scores have several limitations like utilizing prehospital sample, focus on only hypotension or hypoxia as a predictor of difcult airway, and assessing exhaustive laboratory parameters, which make it use cumbersome in the emergency department [11][12][13].
Terefore, there is a need to derive and validate a score that should address physiological predictors in a critically ill adult patient undergoing endotracheal intubation to predict risk of serious outcomes.Te goal of this investigation is to validate the physiological difcult airway score to predict serious outcomes among critically ill adults needing endotracheal intubation in the emergency department.

Study Design and
Setting.Tis is a prospective cohort validation of DAPS at the emergency department of Aga Khan University Hospital from 2021 to 2022.Te recruiting center is an urban, academic 62-bedded emergency department that receives 60,000 patients annually.Te inclusion criteria were all adult patients (≥18 years) who presented to the ED and require endotracheal intubation.Patients with oropharyngeal tumors that require advance airway measures due to the distorted anatomy, patients with out-of-hospital cardiac arrest or ongoing CPR, and pregnant females due to the varied physiological derangements were excluded from the study.Te criteria for intubation were severe respiratory distress, worsening hypoxia not responding to noninvasive positive pressure ventilation, Glasgow coma scale less than 8, anticipated decline (intubation based on physician discretion), and impending airway compromise.We estimated our sample size to be 268 based on absolute precision of 6% with 95% confdence interval and at 5% level of signifcance.Te sample size was calculated from a study by Smischney et al. by WHO calculator showing a 52% rate of postintubation hypotension [14].

Data Collection. Patients requiring intubation in the ED
were identifed either at the triage or by the resuscitation room physicians, who subsequently informed the research assistant.Te research assistant screened patients after taking a verbal consent either from the patient (with intact capacity, which was understanding, appreciation, reasoning, and expression of choice with regard to the process that was followed in the study) or the accompanying decision maker, which was later followed by a written consent.Te preintubation vitals at the triage along with demographic variables were gathered during assessment.Te research assistant did not interfere in the management of the patients needing endotracheal intubation.Te data were collected on a pretested questionnaire.Te pretest was done on 10 questionnaires, which were not included in the fnal analysis.Te data collected on the form were reviewed by the physician who was involved in endotracheal intubation to review any missing data.Presentation symptoms, presentation vital signs, reason for intubation, difcult airway assessment, drugs used in endotracheal intubation, and other procedural data were collected.Te questionnaires were periodically reviewed by the principal investigator for accuracy.Follow-up of the intubated patients was done in the ED at 15 minutes and 1 hour postintubation for record of vitals.Te estimated risk for serious outcomes for diferent DAPS categories was not mentioned on the questionnaire, to prevent physicians from making disposition decisions based on the risk score.To maintain good reporting practice, the TRIPOD checklist was used [15].

Serious
Outcomes.Te primary outcomes were hypotension (defned as a drop in systolic blood pressure <90 mmHg) and hypoxia (defned as oxygen desaturation <92% within 1 hour of intubation).Te secondary outcomes were cardiac arrest (defned as the absence of pulse after endotracheal intubation in the emergency department) and mortality (defned as death occurring within 1 hour after intubation in the emergency department).All the above outcomes were measured at diferent points in time: immediately postintubation, at 15 minutes, and at 1 hour postintubation.

Statistical Analysis.
Data were entered into the Redcap, and data collection and data entry functions were analyzed using SPSS-22 (IBM, IL, USA) and Python 3.8.14.We describe the study patients using means, ranges, and standard deviations as appropriate for continuous variables and frequencies with proportion for categorical variables.Shapiro-Wilk's test was applied to check the quantitative variable's age normality.Te χ 2 test was used to compare proportions.Te association among hypotension, desaturation, cardiac arrest, mortality, and various demographic, clinical, and laboratory characteristics was evaluated using the chi-square or Fisher's exact test or an independent sample t test or Mann-Whitney U test, as appropriate.Te prospective validity of the Difcult Airway Physiological Score was determined by plotting the ROC curve with 95% confdence interval (CI).Te major discriminating point of the DAP score was established by computing Youden's J statistic, sensitivity, specifcity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confdence intervals at diferent score thresholds.A p value of 0.05 was considered statistically signifcant in all analyses.
2.5.Derivation of the Score.Te score was retrospectively derived through a sample of 1021 patients who had endotracheal intubation from January 2016 to December 2020.

Emergency Medicine International
Te sample was divided into development and validation datasets by the train-test split method.A total of 812 (80%) samples were randomly assigned to the development dataset and the remaining 209 (20%) to the validation dataset.Distribution of data on 38 selected system-related and patient-related factors was not statistically diferent between the development and validation groups, respectively.In the modeling-ftting phase, 27 signifcant independent predictors for physiological difcult airway were identifed.Te identifed factors were taken with adjusted OR (95% CI).  1.Additional information regarding the derivation of the score can be found in the published manuscript [16].[15.2%], p value 0.001.Te blood pressure and oxygen saturation trends as per the Difcult Airway Physiological Score showed a major drop in both systolic and diastolic blood pressures in the high-risk group.Te systolic blood pressure, diastolic blood pressure, and oxygen saturation trends between high-risk and low-risk groups as per DAPS with p value are shown in Appendix 2 as supplementary Figure 1.Emergency Medicine International 3.4.Sensitivity Analysis.In the ROC curve analysis, the AUC of the DAPS was found to be 0.864 (95% CI 0.71-0.84)as shown in Figure 2(a).In the ROC curve estimation of diferent score thresholds, a DAPS of >10 has a signifcant area under the curve compared to others as demonstrated in Figure 2(b).Good relation was observed between the observed versus the predicted rate of physiological difcult airway high risk/low risk in the development dataset as per the Hosmer-Lemeshow goodness of test by decile of predicted risk.Te optimal cutof value for the DAPS was found to be a score of ≥10, at which sensitivity of 78.5% (71.7% to 84%), specifcity of 77.9% (70.7% to 83.8%), PPV of 80% (81.20% to 91.19%), NPV of 76% (50.37% to 65.53%), and accuracy of 78.2% were observed.Te sensitivity analysis table of the score with the score threshold value at different score cutofs is shown in Appendix 1 as supplementary Table 1.

Patient
Te total number of true positives and true negatives at a score >10 was 78% as shown in the heat map in Appendix 3 as supplementary Figure 2.

Discussion
In this single-center cohort study, we validated the Difcult Airway Physiological Score on a new cohort of patients who underwent endotracheal intubation in the emergency department.Our study confrmed the accurate model performance characteristics of the original decision tool.Te 12-variable score is easy to use and relevant to the current practice of emergency medicine with special consideration to low-middle-income countries where the burden of critically ill patients is massive due to a weak primary healthcare system.Te results of our study showed that patients with score of 10 or more are at high risk of having serious outcomes postintubation in the emergency department.In our validation study, the Difcult Airway Physiological Score showed a satisfactory discriminative power with high Emergency Medicine International sensitivity and specifcity.Te AUC for the DAPS was 0.864, which shows a need to pay particular attention to these patients requiring intubation in the emergency department.
Te study results emphasize the importance of a priori resuscitation in such cases as it will make the situation worse on intubation.However, there will be instances where crash intubation is done in the resuscitation room and endotracheal intubation is performed at the earliest.Postintubation hypotension is a well-known complication of endotracheal intubation that is reported in the literature [4,13,14].It is associated with high mortality and extended ICU care.Terefore, timely assessment and intervention is paramount [17].Our score demonstrates that with an increasing score, the risk of serious outcomes increases.Te sensitivity analysis reveals a cutof score of 10 based on which we have divided the cohort into high risk and low risk.Tis has resulted in a signifcantly high proportion of patients exhibiting physiologically difcult airway having serious outcomes on endotracheal intubation.Te reason can be due to increase in presentation of critically ill patients, poor primary healthcare system, and healthcare cost borne by the patient, which results in delayed presentation.Furthermore, being a private healthcare setup, the presentation of the patients is late, which results in increase severity of disease on emergency department presentation.
Postintubation hemodynamic instability is a commonly reported occurrence in the ICU setting as well, in which disease severity parameters tend to dominate [5].Te incidence of postintubation hypotension in ICUs is reported between 20% and 46% for critically ill patients, who are associated with poor outcomes when intubated [18].Additionally, our study fndings are in accordance with hypotension prediction tool, which states that peri-intubation hypotension increases the risk for adverse clinical events [13].Tis study was conducted in the ICU, and the tool validity in emergency setting was not done.Advanced age is one of the predictors, and majority of the cohort with a score of 10 and above had age of 45 years and above.Moreover, postintubation cardiac arrest is common in our cohort of patients.One possible explanation is that these individuals were recruited during the COVID pandemic, when the percentage of critically ill COVID patients was high and serious outcomes were more prevalent.Due to a lack of ICU beds, these patients had to wait for several hours in the emergency department after being intubated; as a result, the emergency room seems to have high frequency of serious outcomes, which may be connected to their illness process.
Te unanticipated difcult endotracheal intubation is a common occurrence in the emergency room and a major source of concern for both the emergency attendings and  6 Emergency Medicine International anesthesiologists [3,19,20].It is hence incumbent to identify a score that is quick, easy to apply, and equally sensitive and specifc, to accurately predict serious outcomes in potentially physiologically difcult endotracheal intubations.Te physiological disturbances that are evaluated in our sample were hypotension, hypoxemia, shock index, and pH.Te evaluation of right heart failure, which is one of the variables associated with decompensation, was not conducted due to the variability in bedside ultrasonography that relies on the operator's skills.Additionally, the use of point-of-care ultrasound (POCUS) in our environment is still in the early stages of development.Te strengths of this study include the systematic data collection and prior plan to minimize anticipated bias due to its prospective nature.Additionally, this is the frst study that focuses physiological instability variable assessment in the emergency department.Our score is practical in the daily clinical practice as it is based on presentation clinical variables and a single point-of-care test, which should not have a negative efect on the time management in such difcult scenarios.In summary, this is one of the few studies that have investigated the physiological variables and their association in predicting serious outcomes in critically ill adult patients in the emergency department.Te data are from a tertiary care hospital of a developing world emergency department that is a valuable addition to know the patient presentations in a developing world emergency department.We believe that a patient with physiological instability identifed early and subsequently managed may result in improved patient outcomes and better patient safety.A multicenter validation study is needed to evaluate its use as an adjunct in predicting serious outcomes among patients with physiological instability in the emergency department.
4.1.Limitations.Tere were several limitations in our study.First, it is a single-center study and will need external validation through a multicenter study.Second, the data collection of the study coincided with the COVID-19 pandemic, and there were some changes in the intubation norm like the use of video laryngoscopy, use of respirators and face shield, increased prevalence of resistant hypoxia, and changes in bag-mask ventilation techniques that have signifcantly infuenced the intubation process but could not be determined precisely and were not factored in this study.Tird, the study did not collect data on direct longterm consequences of adverse peri-intubation events on specifc patient's outcomes (e.g., hypoxic brain injury).However, the aim of the study was to prospectively collect data on immediate adverse events.Fourth, interpretation of results may be biased by residual or unmeasured confounders (drugs for rapid sequence intubation, comorbid, and disease severity status).Te residual confounders may have infuenced the higher incidence and severity of adverse events in some subgroups of critically ill patients.We tried to control these confounders through our statistical analysis.Lastly, our study did not investigate DAPS and its impact on clinical care to improve patient's outcome.

Conclusion
Te Difcult Airway Physiological Score (DAPS) was validated to predict the risk of serious outcomes among critically ill adult patients undergoing endotracheal intubation in the emergency department.Our score demonstrates good sensitivity, specifcity, and accuracy in predicting the risk of serious outcomes on patients with physiological difcult airway.
reviewed and edited the manuscript, and proposed the methodology.Asad Iqbal Mian reviewed and edited the manuscript, validated the study, proposed the methodology, and conceptualized the study.

Figure 2 :
Figure 2: (a) Receiver operating characteristic (ROC) curve for the Difcult Airway Physiological Score (DAPS) with an area under the curve at 0.864 and (b) receiver operating characteristic (ROC) curve showing the area under the curve at diferent score thresholds.
Te Difcult Airway Physiological Score was used to divide our study sample into high risk (DAPS ≥10) 194, mean age of 52 (SD � ± 18) years, and low risk (DAPS <10) 132, with a mean age of 47.7 (SD � ± 17.4) years.Te study sample division as per Difcult Airway Physiological Score is shown in Table3.Majority of the patients were falling in the age group of ≥45 years in both high-and low-risk groups.Te association between age group and risk group was found to be highly signifcant (p value<0.001).Many of the intubations were performed in the morning hours (8AM to 4PM), 66 [34%], followed by evening (4PM to 10PM), 64 [33%] in high-risk group, while it was 70 [53%] in low risk where most of the intubations were performed at night (10PM-8AM), p value <0.001.Te main reason for intubation in high-risk group was respiratory distress 169 [87.1%], followed by coma, 132 [68%], and hypoxia, 101 [52.1%].On the contrary, in the low-risk group, the indication was coma, 88 [66.7%], followed by respiratory distress, 70 [53%], and anticipated decline, 59 (44.7%).Te shock index was ≥0.9, which was observed in 128 [66%], whereas it was <0.9 in majority in the low-risk group, 111 (84.1%), p value <0.001.In Difcult Airway Physiological Score ≥10, pH was <7.3 in 70 [36.1%]compared to 4 [3%] in the score of <10, p value <0.001.3.3.Outcome Analysis.Hypotension was the most observed serious event among patients undergoing endotracheal intubation 132 [40.5%], followed by death within 1 hour after intubation in 82 [25.2%] and oxygen saturation <92% in 80 [24.5%].Risk stratifcation of serious outcomes as per the Difcult Airway Physiological Score is shown in Table 4. Cardiac arrest was present in 56 [17.2%], of which 45 [23.2%] was in high risk and 11 [8.3%] were in low risk, p value <0.001.Hypotension was the most serious outcome in the high-risk group 100 [51.5%] compared to 32 [24.2%] in low-risk group, p value <0.001.Desaturation was observed more in high-risk group 60 [30.9%] compared to low-risk group 20 Characteristics.A total of 335 patients were eligible to participate in the study, of which 326 patients were included in the fnal analysis.Te enrollment of study participants is shown in Figure1.Nine patients were excluded due to cardiac arrest prior to intubation, lack of consent because of lack of capacity by the patient or unwilling to participate in the study by the decision

Table 2 :
Characteristics of patients having endotracheal intubation in the emergency department (n � 326).

Table 3 :
Emergency department intubation characteristics among patients as per difcult airway physiological score status.

Table 4 :
Risk stratifcation of serious outcomes as per difcult airway physiological score.